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Viral Couriers

A virus is like a smart bomb, its protein shell a warhead containing DNA or RNA that can subvert a cell's genetic machinery. Now researchers describe in today's issue of Nature how this vehicle might be put to peaceful use, delivering drugs into cells.

Trevor Douglas, a materials scientist at Temple University, spent many years assembling molecules that could be cradled inside ferritin, a protein that shuttles iron around the body. The problem with ferritin, he says, is that it only comes in one size. Then a few years ago, Douglas saw a cartoon of a hollow virus coat and realized that it could serve as a versatile container for molecules. With hundreds of known viruses, he says, "we have an entire library of shapes and sizes." Douglas teamed up with virologist Mark Young of Montana State University in Bozeman to tinker with making empty shells of the cowpea chlorotic mottle virus (CCMV).

CCMV, which normally mottles the leaves of cowpea plants, is a polyhedron, or many-sided ball. When the pH of a solution is higher than 6.5, the CCMV coat swells by 10%, opening up 60 holes about 2 nanometers in diameter. The researchers put empty virus heads, called virions, and particles of a well-known molecule called tungstate in a solution at above pH 6.5, and the tiny tungstate orbs flowed inside. After lowering the pH below 6.5, the holes in the virions closed, trapping tungstate inside. A researcher who wants to use the virus head to transport a drug could tailor the virion to meet the molecule's needs, Douglas says.

Using virions for drug delivery "is a neat concept," says Paul Robbins, a molecular geneticist at the University of Pittsburgh Medical School. However, he points out, several hurdles remain--including how to work with viruses that don't swell and contract in changing pH, and how to trick the immune system to not attack virions. "The work is pretty much a proof of concept at this point," Douglas says.